A Drug to Live Longer? Yes! (But Only If You’re a Fat Mouse)

What would you give to stave off aging? Better yet, what if you could live longer and healthier even while eating to your heart’s content and becoming obese?

That’s what a group of mice in the labs of Rafael de Cabo at the National Institute on Aging have done, thanks to a dose of SRT-1720.

The experimental agent, which in different forms is also being tested in humans, prevented some of the life-shortening diseases associated with obesity in mice, by curbing levels of fat in the liver and improving sensitivity to insulin. SRT-1720 is based on the naturally occurring compound resveratrol, found in red wine, which is thought to combat some of the effects of aging by boosting levels of proteins called sirtuins. These are the proteins that have been associated with 30% life extension in mice and rats put on low-calorie diets.

SRT-1720 was developed by David Sinclair, a biologist at Harvard Medical School and one of the co-authors of the current mouse study, which appears in the new journal Scientific Reports.

But as appealing as it may sound to start downing gallons of resveratrol-rich red wine to stay young, in its natural form the agent hasn’t shown much effect in extending the lives of lab animals. Until now, neither has Sinclair’s synthetic version, SRT-1720, which is made by a company he founded, Sirtris. But in obese mice, the agent appears to have a measurable effect, extending life by 44%, compared with obese mice that didn’t get the drug.

Sirtuins have proved to be highly interesting proteins, but the goal of extending life span was set back last year when extensive trials of resveratrol showed it did not prolong mice’s lives, although it seemed to do them no harm. Another blow came in 2009, when biologists at Pfizer reported that SRT-1720 and other resveratrol mimics did not activate sirtuins and did not have any beneficial effects in fat mice.

The report by Dr. de Cabo and his colleagues may do much to rescue SRT-1720 from this shadow. They found that SRT-1720 offered substantial benefits to the fat mice, with no signs of toxicity. Unlike the Pfizer study, which was short term, they followed large groups of mice for over three years.

In the new study, SRT-1720 appeared to give obese mice the physiology of much leaner animals, which spared them from some of the negative health effects of excess weight. But the scientists note that while these mice lived longer than untreated obese mice, they didn’t live nearly as long as untreated, normal-weight animals.

Further, when the researchers looked at the maximum life span of the SRT-1720-treated fat mice, it wasn’t much different from that of untreated obese mice. That means that the drug may just help animals enjoy more of whatever life they have, rather than actually extending it by any significant amount.

Still, the biology of what’s going on in the bodies of the mice during those intervening years is both interesting and important to researchers who study aging and obesity. If the results are repeated and they hold up, the finding could be the first step toward the ultimate victory in the war against weight — being able to have our cake and eat it too.